Malaria has a tremendous impact on human health, killing millions annually and the disease is a major impediment for social and economic development of nations in malaria-endemic areas, particularly in sub-Saharan Africa (Sachs & Malaney (2002) Nature 415:680-85). Malaria is a mosquito-borne disease that is transmitted by inoculation of the Plasmodium parasite sporozoite stage. Sporozoites invade hepatocytes (Kappe et al (2003) Trends Parasitol. 19:135-43), transform into liver stages, and subsequent liver stage development ultimately results in release of pathogenic merozoites (Shortt & Garnham (1948) Nature 161:126).
Because an effective “subunit” malaria vaccine has remained elusive and the complexity of the malaria parasite Plasmodium might preclude the successful development of such a vaccine, whole organism vaccine approaches against malaria have lately found renewed interest (Hoffman (2004) Nature 430:940-941). The feasibility of such a vaccine has been demonstrated in animal models and subsequently in humans by induction of sterile protective immunity through inoculation with irradiation-attenuated parasites (Nussenzweig et al. (1967) Nature 216:160-62; Hoffman et al. (2002) J. Infect. Dis. 185:1155-64). Liver stages are a prime malaria vaccine target because they can be completely eliminated by sterilizing immune responses, thereby preventing malaria infection (Hoffman & Doolan (2000) Nat. Med 6:1218-9). The recent availability of complete Plasmodium genome sequences (Gardner et al. (2002) Nature 419:498-511; Carlton et al. (2002) Nature 419:512-9) may now permit the development of live-attenuated parasites by more precise and defined genetic manipulations (WO 2004/045559 A2).
Using expression profiling, we identified genes that are specifically expressed during the pre-erythrocytic part of the parasite life cycle (Matuschewski et al. (2002) J. Biol. Chem. 277:41948-53; Kaiser et al. (2004) Mol. Microbiol. 51:1221-32). A number of pre-erythrocytic genes named UIS (up-regulated in infective sporozoites) also showed up-regulation in sporozoites when they gain infectivity for the mammalian host (Matuschewski et al. (2002) J. Biol. Chem. 277:41948-53).
Often overshadowed by Plasmodium, other organisms within the phylum Apicomplexa, as well as protozoan organisms within the phylum Kinetoplastida, cause significant diseases in humans and animals. For example, protozoan organisms within the genuses of Toxoplasma, Neospora, Eimeria, Theileria, Babesia, Cryptosporidium, Sarcocystis, Leucocytozoon, Leishmania, and Trypansoma all devastate susceptible vertebrate host populations and severely impact economic development in endemic regions. In general, these protozoan organisms are eukaryotic, unicellular, parasit that have a life cycle including at least two infective stages in a susceptible vertebrate host, one of which cause the secondary infection that is the hallmark of the protozoan disease.
There is a need in the art for vaccines that protect against protozoan diseases. The present invention addresses this need and others.